ABSTRACT Zika virus (ZIKV) infection with its devastating impact on neurological development of fetuses is already a major health problem in South and Central America, and is likely to impact parts of the USA. Reliable diagnostic tools for ZIKV are vital since ZIKV-infected individuals display either no symptoms or nonspecific symptoms similar to other, more common, viral infections. These diagnostic tools are also essential for management of risks during pregnancy; assessing efficacy of vaccines and therapies; tracking the spread of the infection, tracking ZIKV effects on fetal development; assisting in eradication efforts; and assuring the safety of blood supply. Currently, according to the CDC, no reliable diagnostic tools for ZIKV are available and pipeline technologies are mostly focused on methods suitable for centralized laboratories and inappropriate for resource poor settings and the point of care. This collaborative effort between the University of Pennsylvania and the Instituto Conmemorativo Gorgas de Estudios de la Salud (ICGES) in Panama will research and develop a hybrid, inexpensive, point of care system for combined molecular detection of ZIKV and of antibodies against the ZIKV in oral samples. The proposed system can be used in the clinic, doctor and dentist office, and at home with minimal instrumentation and (optionally) without electrical power. To reduce cost, enable quantification, the system utilizes a smartphone for signal detection, processing, and communications. The system, in its proposed form, is suitable for individual diagnostics, but is amenable to concurrent processing of large numbers of samples. The Penn team will develop the assays: reverse transcription isothermal enzymatic amplification (RT-LAMP) of viral nucleic acids with visual detection of amplicons and an immunoassay to monitor separately antibodies interactions with ZIKV and dengue virus (DENV) antigens to improve assay specificity; and the necessary hardware. ICGES will verify system's performance and ease of use with samples of ZIKV patients in Panama.